Nerve roles in blastema induction and pattern formation in limb regeneration.

Compared to amniotes, amphibians are widely known to be great healers. Urodele amphibians in particular have tremendous regeneration abilities, and can even regenerate organs, such as the brain, the heart and the limbs. Limb regeneration, in particular, has been investigated since it is representative of their superior regeneration abilities, and the presence of nerves has been examined in detail because they play essential roles in limb regeneration.

Hyperinnervation improves Xenopus laevis limb regeneration.

Xenopus laevis (an anuran amphibian) shows limb regeneration ability between that of urodele amphibians and that of amniotes. Xenopus frogs can initiate limb regeneration but fail to form patterned limbs. Regenerated limbs mainly consist of cone-shaped cartilage without any joints or branches.

FGF and BMP derived from dorsal root ganglia regulate blastema induction in limb regeneration in Ambystoma mexicanum.

Urodele amphibians have a remarkable organ regeneration ability that is regulated by neural inputs. The identification of these neural inputs has been a challenge. Recently, Fibroblast growth factor (Fgf) and Bone morphogenic protein (Bmp) were shown to substitute for nerve functions in limb and tail regeneration in urodele amphibians.

Cooperative inputs of Bmp and Fgf signaling induce tail regeneration in urodele amphibians.

Urodele amphibians have remarkable organ regeneration ability. They can regenerate not only limbs but also a tail throughout their life. It has been demonstrated that the regeneration of some organs are governed by the presence of neural tissues.

Comparative Analysis of Cartilage Marker Gene Expression Patterns during Axolotl and Xenopus Limb Regeneration.

Axolotls (Ambystoma mexicanum) can completely regenerate lost limbs, whereas Xenopus laevis frogs cannot. During limb regeneration, a blastema is first formed at the amputation plane. It is thought that this regeneration blastema forms a limb by mechanisms similar to those of a developing embryonic limb bud.

Regeneration inducers in limb regeneration.

Limb regeneration ability, which can be observed in amphibians, has been investigated as a representative phenomenon of organ regeneration. Recently, an alternative experimental system called the accessory limb model was developed to investigate early regulation of amphibian limb regeneration. The accessory limb model contributed to identification of limb regeneration inducers in urodele amphibians.

Co-operative Bmp- and Fgf-signaling inputs convert skin wound healing to limb formation in urodele amphibians.

Urodele amphibians have remarkable organ regeneration capability, and their limb regeneration capability has been investigated as a representative phenomenon. In the early 19th century, nerves were reported to be an essential tissue for the successful induction of limb regeneration. Nerve substances that function in the induction of limb regeneration responses have long been sought.

Implication of two different regeneration systems in limb regeneration.

Limb regeneration is a representative phenomenon of organ regeneration in urodele amphibians, such as an axolotl. An amputated limb starts regenerating from a remaining stump (proximal) to lost finger tips (distal). In the present case, proximal-distal (PD) reorganization takes place in a regenerating tissue, called a blastema.

Ectopic blastema induction by nerve deviation and skin wounding: a new regeneration model in Xenopus laevis.

Recently, the accessory limb model (ALM) has become an alternative study system for limb regeneration studies in axolotls instead of using an amputated limb. ALM progresses limb regeneration study in axolotls because of its advantages. To apply and/or to compare knowledge in axolotl ALM studies to other vertebrates is a conceivable next step.

Nerve independent limb induction in axolotls.

Urodele amphibians can regenerate their limbs. During limb regeneration, dermal fibroblasts are transformed into undifferentiated cells called blastema cells. These dermis-blastema cells show multipotency.